Browsing by Subject "Genetica molecular"

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    Mecanismos de señalización del estrés foto-oxidativo y oxidativo en Myxococcus xanthus: implicaciones funcionales y perspectivas evolutivas
    (Universidad de Murcia, 2025-07-28) Rey Navalón, Irene del; Elías Arnanz, Montserrat; Sin departamento asociado; Escuela Internacional de Doctorado
    Myxobacteria, recently reclassified into Myxococcota phylum, are Gram-negative, non-pathogenic, aerobic bacteria. The best-studied species is Myxococcus xanthus, whose light response has been well characterized by our research group. M. xanthus has two pathways to respond to light, both leading to carotenoid biosynthesis, whose antioxidant properties protect cells against photooxidative stress. The more complex pathway depends on protoporphyrin IX and 1O2, and the activity of the σ-ECF/anti-σ pair CarQ/CarR. CarF is a key membrane protein in the response to light in M. xanthus. This protein has been a long-sought enzyme, whose activity has been unknown for more than fifty years. The study of CarF led to the discovery of its fatty acid desaturase activity (PEDS1), which is responsible for the introduction of the characteristic vinyl-ether bond in the sn-1 position of plasmalogens. Plasmalogens are a special type of glycerophospholipid whose unique structural and functional properties are due to the presence of their vinyl-ether bond. Alterations in their levels have been linked to the development of different human diseases, from Zellweger syndrome to neurodegenerative diseases such as Alzheimer’s or Parkinson’s, and cancer. They present a patchy distribution across the Tree of Life: among bacteria, they are present in anaerobic and facultative bacteria, and among aerobic bacteria, their presence is restricted to myxobacteria. They are also present in mammals and protists but absent in plants and fungi. Their atypical distribution pushed us to study the functional and evolutionary parallelisms between myxobacteria and mammals. The peroxisomal enzymes FAR, AGPS and GNPAT are key in the plasmalogen biosynthesis pathway in mammals. In contrast, M. xanthus has two pathways responsible for plasmalogen precursor synthesis. The main pathway (ElbA-E), where ElbD is a multifunctional enzyme, whose FAR and GNPAT activities are essential. The auxiliary pathway involves a three-gene operon (MXAN_1676-1674), in which MXAN_1675 has FAR and GNPAT domains, also essential for function. The functional study of elbA-E genes confirmed that elbB, elbC, and elbD are key for ether lipid and plasmalogen biosynthesis, being elbA and elbE (SDR activity) make plasmalogen biosynthesis more efficient. Given the similarities between the pathway in mammals and M. xanthus, another objective of the present work has been the study of the origin and distribution of this pathway, which has been developed in collaboration with Prof. Iñaki Ruiz Trillo research group. The results point out that myxobacteria could be responsible for horizontal gene transfer (HGT) events to eukaryotes, which highlights the value of myxobacteria as a model organism to study eukaryotic-like mechanisms. The study of the photooxidative stress response in M. xanthus revealed the presence of new CarQ-dependent genes, MXAN_6864 y el operon MXAN_6048-6047 encoding two putative methionine sulfoxide reductases (Msr). Their discovery as new CarQ-dependent genes establishes a novel link between photooxidative damage and protein repair. Even though the light response has been well-characterized, their response mechanisms to other stresses, such as peroxide stress, have not been studied. The canonical regulators against peroxide stress are OxyR and PerR, but M. xanthus lacks both canonical regulators. Instead, it uses a novel regulator called PexR (Peroxide stress Regulator), a bacterial enhancer binding protein which is needed to initiate σ54-dependent gene transcription. PexR directly regulates the expression of the peroxiredoxin AhpC and the catalase KatB, as assessed by ChIP-qPCR. PexR binds metal (either Zn2+ or Fe2+) by His, Cys and Asp residues located at its N-terminal GAF domain, which plays an autoinhibitory role in the absence of H2O2. The proposed mechanism of action of PexR relies on metal expulsion and protein oxidation upon H2O2 exposure.